(P 50) A NEW MURINE MODEL OF DEDIFFERENTIATED LIPOSARCOMA DEFINED BY HIGH PROLIFERATION AND METABOLIC ADAPTABILITY

Objective: Dedifferentiated liposarcoma (DDLPS) is a high grade soft tissue sarcoma with limited treatment options. We derived two cell lines from autochthonous adipocyte-CreTrp53f/f;Ptenf/f (ACPP) tumors which develop orthotopic DDLPS tumors in WT C57BL/6 mice. These cell lines recapitulate histological and transcriptional alterations observed in DDLPS in patients. Our aim was to elucidate the phenotypic and molecular differences between the cell lines to enhance their utility as reliable preclinical models for studying DDLPS.

Methods: We used HoloMonitor M4, a digital holographic microscope, to track live cells’ morphometric and optical features over time. We performed bulk RNA-seq and compared two ACPP-derived DDLPS cell lines, N1011 and N1018, by gene set enrichment (GSEA) Hallmark pathway analysis.

Results: Each DDLPS cell line exhibit distinct morphology, cell characteristics, and dynamics. In terms of morphology, N1018 shows greater heterogeneity in cell size, volume, optical density, and surface features, consistent with the metabolic plasticity required for rapid division and higher motility (28% higher than N1011). Hallmark GSEA revealed strong activation of the E2F, MYC-I/II, G2M-checkpoint, and mitotic-spindle programs in N1018, supporting the higher proliferation rate (65% above N1011). In addition, pathways tied to rRNA metabolism, 5.8 S-rRNA maturation, cytosolic and mitochondrial translation, and RHO-GTPase signaling were elevated in N1018, indicating enhanced ribosome biogenesis, actin remodeling, and metabolic flexibility. In contrast, N1011 displayed a more uniform, lower-intensity optical and morphometric values, stable surface features, and balanced internal organization.

Conclusion: These results suggest that the N1018 cell line could serve as a model for studying mechanisms underlying rapid proliferation, invasion, and potential treatment resistance in aggressive DDLPS, providing a valuable platform for preclinical therapeutic development.